The present invention is directed to an angiogenic factor, pharmaceutical formulations comprising effective amounts of the angiogenic factor and methods of use thereof as a wound healing agent.
The course of wound healing can be influenced pharmacologically. Dietary compounds, such as vitamins A and C, zinc, protein, as well as oxygen, can have a direct influence on the course of wound healing. Addition of any one of these compounds to a wound otherwise deprived of that compound will augment aspects of the healing of that wound.
Growth factors are believed to promote wound healing. For example, epidermal growth factor (EGF) present in saliva is believed to accelerate wound healing in mice. Schultz, G. S. et al. (Science 232:350-352, 1986) reported that transforming growth factor (TGF)-alpha and vaccinia virus growth factor (VGF), both of which are substantially homologous to EGF, accelerated epidermal wound healing in pigs when topically applied to second degree burns and were significantly more active than EGF.
Also known are a variety of angiogenic (literally "blood-vessel-forming") growth factors, such as fibroblast growth factors (FGFs) which are believed to promote growth and organization of endothelial cells (which line blood vessels) into new blood vessels. Preliminary evidence indicates that the two known (sequenced) angiogenic growth factors, basic and acidic FGF (so named due to the total net charge on the molecules) may be of use as wound healing agents.
Angiogenesis is an essential part of wound healing. Angiogenesis can be described as the directed outgrowth of new capillaries towards a specific stimulus. Under microscopic evaluation, endothelial cells (cells which line blood vessels) can be seen to migrate from the tip of the capillary before any induction of mitosis (or cell division).
Skin Respiratory Factor (SRF) is an aqueous alcoholic extract of Brewer's Yeast (Saccharomyces cervisiae). SRF has been employed as a wound healing agent and is an ingredient in a proprietary hemorrhoidal medication (Preparation H.RTM.).
Goodson, W. et al. (J. Sur. Res. 21:125-129, 1976) disclosed the augmentation of some aspects of wound healing by SRF. SRF increased the in vitro synthesis of collagen by human skin homogenates, the consumption of oxygen by cultured fibroblasts, and augmented epithelialization of moist open wounds in rabbits.
Subramanyan, K., et al. (Dig. Dis. Sci. 29: 829-832, 1984) disclosed a beneficial effect of a pharmaceutical preparation containing SRF upon the healing of artificially induced ulcers.
Kaplan, J. Z. (Arch. Suro. 119: 1005-1008, 1984) conducted a double blind randomized study of 26 human skin graft donor sites. Kaplan reported that earlier angiogenesis and epithelialization occurred in those sites treated with an ointment containing the above-mentioned yeast factor compared with donor sites in the same patients which were treated with a control ointment. Kaplan referred to the material he used as "Live Yeast Cell Derivative" (LYCD). LYCD was prepared in the exact same manner as SRF.
Mazarin, U.S. Pat. No. 4,575,457 issued Mar. 11, 1986, disclosed pharmaceutical compositions comprising SRF which were said to provide effective therapy for gingivitis when brushed on the teeth and gingivae.
The SRF employed in the above-mentioned publications was the crude alcohol-extracted material obtained from live yeast cell derivatives (LYCD). SRF is a dark brown viscous fluid and it is not known which of its many components are responsible for the various biological activities contained therein. No one has previously fractionated this material in order to identify the active (or any) factors present therein. There is a need in the art for improved wound healing compositions which can be used to treat mammals suffering from wounds such as hemorrhoids, decubitus ulcers (bed sores), other wounds or burns. As SRF has been used safely and effectively in a proprietary over the counter wound healing medication for over forty-five years, its use in a purified form would be expected to be highly efficacious.
Therefore, it is an object of the present invention to identify the active wound healing principle(s) in SRF.
It is another object of the present invention to fractionate and purify said active principle(s).
A further object of the present invention is to provide pharmaceutical formulations for treating mammals suffering from wounds or burns.
These and other objects of the present invention will be apparent to those of ordinary skill in the art in light of the present description, claims and drawings.